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Sciences Research: New zoonosis centre

Infectious diseases make for regular reading in today’s daily media. A centre in Liverpool may be the key to discovering and preventing diseases both old and new. Roger Highfield explores the work that researchers have ahead of them

The year is 2015 and, thanks to a novel test for disease, the cost of an urban outbreak of the pneumonia-like illness SARS has been cut by more than £200 million. Ten years later, a new strain of killer flu emerges in the Far East, threatening to cause a pandemic. But thanks to a novel range of detection, identification and monitoring, projected death rates in the UK are cut by 90%.

These are some projections of how new technologies could combat the age-old threat of infectious disease. They were made by a recent crystal ball-gazing exercise (see below) involving more than 300 scientists and experts. Their findings do more than anything to underline the importance of the world’s first interdisciplinary centre dedicated to the study of animal-borne diseases that can pass to people, established at the University of Liverpool.

Diseases that affect other creatures are the biggest contribution to new illnesses among people, such as BSE (from cows) and SARS (from palm civets and dog raccoons). Perhaps the most notorious is Aids, which began as a simian virus, one of a family of lentiviruses, and has now spread to people, orphaning three million children in Africa alone and cutting life expectancy in sub-Saharan Africa to fewer than 40 years.

These are all called zoonoses – the term used by scientists to describe diseases that originate in animals but can jump species to infect humans. Liverpool was chosen for the new centre – the National Centre For Zoonosis Research – because it was the only university in Britain with expertise in biological sciences, medicine, veterinary science and tropical medicine. This puts the University in a unique position to conduct detailed interdisciplinary research into these diseases, some of which are the most deadly encountered.

The new centre

What is the biochip?

The biochip is a time-saving gizmo that it is hoped will be able to identify over 600 known viruses that affect animals, plants, fish, bees and any diseases – zoonoses – that jump the species barrier.

The first biochip of its kind will be used as a single test for detecting, identifying, and monitoring multiple viruses, including avian influenza, foot and mouth disease and rabies, according to the Department for Environment, Food and Rural Affairs (Defra). Defra has backed the £1.52-million Detection and Identification of Infectious Diseases project.

The biochip works using microarray technology. The DNA of known viruses is melded onto a glass 'chip' and the DNA of the unknown virus is introduced to the chip, sometimes in a solution.

The DNA from the unknown virus will stick to sections of the fixed DNA if it is matching. The sample is then run through a scan array, which visualises and identifies the virus. The whole process takes a day and a half. Current methods for testing for viruses, for example, H5N1, take up to four days.

One of the key jobs of the new biochip will be to observe and identify new, emerging diseases. This kind of approach was successfully used in identifying that SARS was caused by a type of virus, which is called a coronavirus.

The advantages of having a single test for identifying multiple viruses include:
• In emergencies, it will be helpful to have a single test for identifying the virus, which means the right resources to tackle the virus outbreak can be deployed at an early stage to avoid it spreading further.
• Because the biochip can be used to identify viruses from different species, the barriers between traditional scientific disciplines are broken down. More scientists can do the testing in an emergency situation.
• The biochip will be able to identify diseases that have similar symptoms such as Newcastle disease and bird flu. Researchers are working to make the biochip sensitive to the subspecies of a virus, for example H5, so it will be able to indicate the how lethal the virus is.

Professor Jon Saunders, Pro-Vice-Chancellor of Liverpool, says: 'The new centre will build on our unique expertise in animal and human infectious disease and will further strengthen Liverpool’s capability for studying infections transmitted between animals and people.' The university hopes that, given that it is already a major player in advancing the research base of the northwest of England, it will now boost its international reputation by undertaking research that has a major impact on world health.

The Northwest Development Agency awarded the university £1.7 million towards the establishment of the centre, which will be based at Leahurst in Neston on the Wirral, home of the University’s Veterinary Teaching Hospital. A former veterinary building on the site that has been undergoing a major refurbishment is expected to be opened by next summer.

The initiative, which is a joint venture between the Universities of Liverpool and Lancaster, the Health Protection Agency (HPA) and the Veterinary Laboratories Agency (VLA) has been established, as worldwide, around 75% of human-emerging infectious diseases are zoonoses, yet research in this area, and the advice available to governments and the public, is often incomplete and sometimes contradictory.

Professor Malcolm Bennett, Head of the University’s Department of Veterinary Pathology, and co-director of the new centre, explains that it will stimulate a more joined up approach: ‘At Liverpool, we are able to take a multidisciplinary approach to zoonotic infections and we already undertake research into zoonoses collaboratively with the HPA and the VLA. The centre will provide a core facility and focus for this work.’

The national centre will follow a hub-and-spoke model, farming out work to other centres of expertise, such as the medical statisticians in Lancaster, computer modellers and virologists in Liverpool, and experts and facilities at the Health Protection and Veterinary Laboratories Agencies. The team will also collaborate with researchers overseas: the centre has a field station in Malawi.

Financial issues

The first grant received by the new centre went to Professor Bennett to study the diversity of infections in wildlife. Research teams will also carry out lab-based genetic studies, field studies of the ecology of viruses, and computer-based modelling.

As well as studying the transmission and disease-causing potential of bacteria, fungi and viruses, the scientists are keen to see why some animals and humans are more vulnerable than others to certain diseases.

Tony Hart, Professor of Medical Microbiology in the University’s Faculty of Medicine, and co-director of the centre, says: ‘Our priorities will include the bacteria Campylobacter and E coli O157 – we will be studying the way they move from the animal to the human population via the food chain.

‘We’ll also be looking at the role of wildlife and companion animals. We know that some of these diseases can be transmitted to humans by birds, rodents and even family animals such as dogs and cats.’

In Malaysia, Professor Hart is already following up one discovery made while investigating a bat virus that can infect humans – the Nipah virus. Working with colleagues in Malaysia, he and his colleague Dr Paul Chua found that fruit bats also harbour a chlamydia -like organism, which can infect human cells and be excreted in urine. They’re now trying to work out whether the newly recognised organism, Waddlia malaysiensis, poses a potential threat to people.

One focus of attention for the new centre is bird flu, given fears that the current strain in circulation, H5N1, could mutate or combine with a human strain to spark a pandemic. With the British Wildlife Trust and the British Ornithological Society, the team has been trapping wild birds. One recent expedition to Hilbre Island, off the Wirral, sampled 200 birds for a range of infections.

Complementing this kind of field work will be studies of how the avian virus can adapt to a human host. The avian flu viruses attach to human cells using molecules called receptors. Studies in the Netherlands and Japan suggest that the H5N1 virus binds to sugars on the surface of cells deep in human lungs, but not to cells lining the human nose and throat. This fits the pattern of damage seen in the few autopsies that have been performed on H5N1 victims.

‘The receptor for avian flu is found predominantly in birds but we do have the same receptor – but deep in our lungs, in the alveoli (the delicate sacs, where oxygen enters the blood),’ says Professor Hart. ‘That is why for humans to be infected with H5N1, they need to inhale a big load right into the lungs.’

The result is pneumonia, which can lead to death. But the good news, so far, is that the virus remains locked up deep in the lung. ‘They do not produce a lot of virus when they are coughing out because there is only a small area infected. If that virus could infect the whole of the respiratory tract, from throat to alveoli, then there would be much more virus coming out and it would be more likely to spread.’

Flu normally travels between people by being sneezed out and breathed in through the nose and throat so the poor binding of the H5N1 virus high in the respiratory tract might be why the virus has so far not been able to spread between people – a major factor stopping the current bird flu pandemic from becoming a human pandemic.

Government influence

The need for the kind of initiative that is under way in Liverpool was underlined recently by a report from Foresight, a Government science-based programme led by Sir David King, the Government’s Chief Scientific Adviser. It consulted experts from 30 countries since, as Sir David put it, these diseases have ‘no regard for international barriers’.

Foresight looks beyond normal planning timescales to identify potential opportunities from new science and technologies, producing what the Department of Trade and Industry says are ‘challenging visions of the future’. In this particular case, the project looked at the evolving risk and the changing requirements for detection, identification and monitoring of infectious diseases in plants, animals and humans.

The exercise, which is called the Detection and Identification of Infectious Diseases (DIID) project (more details can be found at ) concluded that current and new infectious diseases will continue to have profound human, economic and social impacts. Unless new ways of sharing research and technological advances are implemented at all levels, the poorest people in the world will continue to suffer in a disproportionate manner.

The report also showed that improved technologies for the detection, identification and monitoring of diseases will help enable faster responses to disease outbreaks, so reducing the risk. It anticipated that:
• in a new influenza emerging in 2025, a range of future detection, identification and monitoring systems could reduce UK mortality from a pandemic by 90%
• in a SARS outbreak in 2015, a new diagnostic test could save £230 million of healthcare costs in a major city outbreak.

Of all the new fields of research, the detection, identification and monitoring of disease, known by the acronym DIM, ‘is a critical part of disease management and the part where science has the potential to deliver very significant new capabilities over the next 10–25 years,’ says Sir David. ‘We have got to anticipate the emergence of entirely new diseases with new properties over that period.’

By some measures, new pathogens ‘emerge about once every eight months,’ he says.

He added that three-quarters of those that make it into people are present in animals. Scientists need better understanding of how diseases emerge and evolve. ‘We need to reduce the unpredictably of the emergence through vigilance,’ says Sir David. ‘We need to model how diseases will spread as a result of travel and trade in our globalised world,’ he added. Climate change will also have an important, though complex, effect on the patterns of disease to spread around the planet.

Now companies and laboratories around the world are looking at a range of relevant technologies, such as efficient gene reading and genomics methods. They range from high-speed, high-throughput lab methods to simple dip sticks that detect disease.

Other opportunities will come from airport scanners and other such non-invasive methods, which can detect a person with a fever, or can spot trace chemicals given off by the body that are linked with illness. There is also a need for held devices that can identify an agent, smart swabs and even colour change lollipops that can be used by anyone of any expertise to track new diseases. These new approaches are not just of interest to Britain, says Sir David.

‘We are talking about the entire world.’

Roger Highfield was Science Editor of The Daily Telegraph newspaper and is now Editor of New Scientist magazine.

Read other science research papers, including 2007 research about The Space Weather Forecast and research from 2008 on Harnessing Power From Nature.